Water-soluble polymers, such as polyethylene glycols (PEGs), have been investigated extensively in recent years for use as biocompatible, protein repulsive, noninflammatory, and nonimmunogenic modifiers for drugs, proteins, enzymes, and surfaces of implanted materials. These characteristics have variously been attributed to a combination of properties of such polymers, e.g., nonionic character, water solubility, backbone flexibility, and volume exclusion effect in solution or when immobilized on a surface.
While extensive efforts have been made to render foreign substances, such as drugs, proteins, and the like, non-immunogenic employing water-soluble polymers such as PEG, the use of such polymers to render an individual cell non-immunogenic has not been considered in the art. If such polymers could be attached directly to a cell surface, then it is possible, due to the exclusion of proteins and macromolecules from the vicinity of the cell surface, that the cell as a whole may be rendered non-immunogenic. The ability to accomplish such attachment would be invaluable for a variety of treatment protocols.
It is known that mammalian cell membranes have a variety of negatively charged species on their exterior. For example, negatively charged proteoglycans (PGA), glycosaminoglycans (GAG), such as chondroitin sulfate and heparin sulfate, and negatively charged lipids have all been identified on cell exteriors. Not surprisingly, polycation species such as polylysine and polyornithine interact with negatively charged cell surfaces to form a strong ionic linkage. Unfortunately, polycations (such as polylysine and polyornithine) are known to be cytotoxic, even at fairly low concentrations. Polylysine, for example, has been used as a cell fixative, and has been shown to cause cell aggregation (e.g., with human platelets).
While water-soluble polymers, having found use in a variety of biological applications, would be ideal for use in treating cells to render them non-immunogenic, their generally non-ionic nature renders them substantially unable to bind to cell membranes. Thus, for example, treatment of cells with unmodified PEG was unable to confer a non-adhesive or protein repellant character on such cells.